A retrospective study of uropathogen and its antibiotic resistance among children with urinary tract infection from a single center in China

Urinary tract infection (UTI) is a well-known bacterial infection posing serious health problem in children. A retrospective study was conducted to explore the uropathogen and its antibiotic resistance in children with UTI. Data of urine culture and antimicrobial susceptibility test was collected. Consequently, 840 children were included. The overall culture-positive UTI was 458 (54.52 %) with Escherichia coli 166 (36.24 %), followed by Enterococcus faecalis 59 (12.88 %), Enterococcus faecium 70 (15.28 %) and others. They were highly resistant to the most commonly used antibiotics. In 694 children with complicated UTI, there were 8 children with fungal infection. Multiple drug resistance (MDR) was recorded in 315 (80.98 %). The overall proportion of Extended Spectrum β-Lactamase (ESβL) production was 25 (6.43 %). In 146 children with simple UTI, MDR were also detected in 47 (77.05 %). There were 6 (9.84 %) positive for ESβL production. Our study found that complicated UTI was relatively common. Escherichia coli was the most prevalent isolate, followed by Enterococcus faecium and Enterococcus faecalis. These organisms were highly resistant to the most commonly used antibiotics. Relatively high prevalence of MDR and low ESβL-producing organisms were observed.


Introduction
Urinary tract infection (UTI) is an infectious disease in children.Approximately 8.4 % of girls and 1.7 % of boys under 7 years are diagnosed with UTI, and up to 30 % of children experience recurrent UTI by the age of 12 months [1,2].The short-term symptoms usually contain fever, dysuria, and flank pain [3].If not properly treated, it often develops recurrent UTI, kidney scar, and decline of renal function [4,5].In contrast to adults, children are susceptible to UTI due to immune disorders, congenital anomalies of the genitourinary tract, and so on [6,7].An indwelling catheter often introduces external pathogens into the bladder.Congenital abnormalities allow for the prolongation of bacteruria and decreasing the clearance of invading pathogens due to poor drainage.
In practice, it is vital to differentiate complicated UTI from simple UTI.The risk factors of complicated UTI include the functional or structural abnormalities of the genitourinary tract, foreign bodies, stones, and immunosuppression.It often leads to treatment failure and serious complications, which may require further evaluation [8].UTI may be a clinical presentation for potential abnormality due to its poor drainage in children [9].In addition, some patients also have UTI with stone disease, and necessitate drainage [10,11].Thus, the therapeutic goals of complicated UTI identify those potentially risk factors [12].The abnormalities often cause inappropriate antibacterial treatment, which in turn increases antimicrobial resistance (AMR) [13].
Rapid administrations of empirical antibiotics are required before urine culture testing.The pathogen is detected and identified in urine which contributes to antibacterial treatment.There is an urgent need to identify bacterial strains and susceptibility to commonly used antimicrobial, as well as potentially risk factors in children.

Study design
A retrospective analysis was performed at the department of Urology, Anhui Provincial Children's Hospital during the 6 years from January 2017 to December 2022.The general characteristics, the microorganism isolated, and the antimicrobial susceptibility profiles were collected.Written informed consents were collected from their parents.

Statistical analysis
A descriptive data was expressed as frequency and its percentage in our study such as the proportion of children, susceptibility patterns, MDR, and so on.In addition, the independent risk factor for culture positive UTI was tested by univariable logistic regression analyses.Data was analysed by SPSS statistical software package (version 16.0).P-value less than 0.05 was taken as statistically significant.
There were 458 culture-positive UTIs.Of these, 450 patients was bacterial infection.MDR were recorded in 362 (80.44 %).Among 397 culture-positive complicated UTI, there were 8 children with fungal infection and 389 children diagnosing bacterial isolates.MDR were recorded in 315 (80.98 %).The presence of ESβL was found in Klebsiella pneumoniae, Klebsiella oxytoca and Escherichia coli isolates.The overall proportion of ESβL production was 25 (6.43 %).Specifically, there were 21 Escherichia coli, 3 Klebsiella pneumoniae and 1 Klebsiella oxytoca positive for ESβL production (Table 5).MDR of simple UTI were also detected in 47 (77.05 %).There were only 6 (9.84 %) Escherichia coli positive for ESβL production.Univariable logistic regression analyses showed significant associations between prevalence of culture positive UTI and age, UTI type (P < 0.05) (Table 6).We found that there were 305, 153 culture-positive UTIs in male and female, respectively.No statistical difference was detected between gender and culture positive UTI (P > 0.05).All the other factors were also not statistically significant.

Discussion
UTIs are found in nearly 0.7 % of girls and 2.7 % of boys by the age of 1 year [15].Moreover, about 5 % of febrile girls and 20 % of febrile boys under two months are diagnosed with UTI [16].UTIs are more common in premature infants than term infants during neonatal period [17].There are 30 % children within 6 months and even up to 50 % school-age girls with recurrent UTI [18,19].The high prevalence of UTI and fear of its recurrence often lead to irrational use of antibiotics.Empirical treatment is also prevalent in primary hospital [20,21].
Complicated UTIs are defined as those infections causing severe complications, such as urosepsis, renal scarring, and end-stage renal disease.Those risk factors in children are stones, indwelling catheters, and abnormalities of the genitourinary tract [22].Anatomical or functional abnormalities allow for the prolongation of bacteruria and decreasing the clearance of invading pathogens due to poor drainage [23].Children with posterior urethral valves (PUV) have increased risks of UTI for voiding dysfunction, elevating    bladder pressure stemming and ongoing renal damage.The continued bladder pressure from urine stasis or obstruction can causes vesicoureteric reflux (VUR) and increases renal function damage by an ascending infection [24].Approximately 20 % of neonatal cases with VUR were diagnosed with UTI and then led to renal scars [25,26].In addition, UTI remains the first cause of morbidity and the second cause of mortality in patients with neurogenic bladder due to high bladder pressure, detrusor exyernal sphincter dyssynergia and post-void residual [27].These children often require clean intermittent catheterisation, which further increase the UTI risk [28,29].It is important to identify these abnormalities early because they may serve as a reservoir for bacterial growth or recurrent infections.UTI is mostly caused by Gram-negative bacillus because of its unique structure which promotes the epithelial cells attachment and prevents bacteria from urinary lavage [30].E. coli is the most predominant bacterium isolated from urine [30].Other common Gram-negative pathogens include Klebsilla pneumoniae, Proteus mirabilis, Enterobacter, Citrobacter, and P. aeruginosa.Besides, Streptococcus species and Staphylococcus species are the frequent Gram-positive bacteria.In the present study, we also found the similar results.
In the group of complicated UTI, we found that Gram-negative isolates were shown high sensitivity to amikacin, ertapenem, nitrofurantoin, imipenem, and cefotetan, and highly resistant to ampicillin, cephazolin, ceftriaxone, trimethoprim-sulfamethoxazole and aztreonam.Gram positive bacteria showed high sensitivity to vancomycin, penicillin-G, tigecycline, linezolid and nitrofurantoin and highly resident to tetracycline, quinupristin and erythromycin.For simple UTI patients, the most common uropathogen was Escherichia coli.It was highly sensitive to ertapenem, imipenem, cefotetan, amikacin and nitrofurantoin and high rates of resistant were also observed to ampicillin, trimethoprim-sulfamethoxazole, cephazolin and ceftriaxone.Majority of the isolates were highly resistant to the commonly prescribed antibiotics.Thus, empirical treatment should be minimized as sensitivity always varies for each organism over time.
For empirical treatments worldwide, AMR is a major problem, especially in regions with limited resources.Presence of MDR organisms was often detected.ESβL producing strains can easily hydrolyze β-lactam agents that the bacteria resist antibiotics.These organisms also carry genes encoding resistance to antibiotics.The presence of ESβL was often found in the members of Enterobacteriaceae family, particularly Klebsiella pneumoniae and Escherichia coli.In the present study, MDR was relatively high in both groups.Complicated UTI organisms showed a relatively higher MDR.In addition, the prevalence of ESβL in children was relative low.ESβL, Extended Spectrum β-Lactamase.MDR, multiple drug resistance.R1, resistance to one drugs.R2, resistance to two drugs.R3, resistance to three drugs.R4, resistance to four drugs.R5, resistance to five drugs.R6, resistance to six drugs.R7, resistance to seven drugs.There are some limitations.Firstly, this study was performed in a single center.Secondly, our study is a retrospective study.Thirdly, some asymptomatic patients in clinic were not included.Eventually, contamination of voided specimens from infants is a problem to be solved.

Conclusion
Our study revealed a higher prevalence of complicated UTI.The majority of the isolates was Gram-negative bacteria.Escherichia coli was the most prevalent isolate followed by Enterococcus faecium and Enterococcus faecalis.These organisms were highly resistant to the most commonly used antibiotics.Relatively high MDR and low ESβL-producing organisms were commonly observed in both groups.Urine culture for antimicrobial susceptibility test is vital for appropriate management of UTI.

Compliance with ethics guidelines
Kaiping Zhang, Xiang Fang, Yin Zhang and Min Chao declare no conflicts of interest.This manuscript is a retrospective study and does not involve a research protocol requiring approval by the relevant institutional review board or ethics committee.

Table 2
Bacterial profile isolated from urine in both simple and complicated UTI.

Table 3
Antimicrobial susceptibility patterns of Gram-negative bacteria from complicated UTI samples.
K.Zhang et al.

Table 4
Antimicrobial susceptibility patterns of Gram-positive bacteria from simple UTI samples.

Table 5
Multi drug resistance pattern and ESβL production of bacterial isolates from children with complicated UTI.

Table 6
Univariablee logistic regression analyses for factors associated with culture-positive UTI among children with UTI.